Clinical Trial Results:
A Multicenter, Double-Blind, Randomized, Comparative Study to Evaluate the Safety, Tolerability, and Efficacy of Caspofungin Versus (Amphotericin B) Liposome for Injection as Empirical Therapy in Pediatric Patients With Persistent Fever and Neutropenia
Summary
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EudraCT number |
2014-005021-13 |
Trial protocol |
Outside EU/EEA |
Global end of trial date |
04 Oct 2006
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Results information
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Results version number |
v1(current) |
This version publication date |
10 Feb 2016
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First version publication date |
15 Jul 2015
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Other versions |
Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
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Trial identification
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Sponsor protocol code |
MK-0991-044
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
NCT00082537 | ||
WHO universal trial number (UTN) |
- | ||
Sponsors
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Sponsor organisation name |
Merck Sharp & Dohme Corp.
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Sponsor organisation address |
2000 Galloping Hill Road, Kenilworth, NJ, United States, 07033
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Public contact |
Clinical Trials Disclosure, Merck Sharp & Dohme Corp., ClinicalTrialsDisclosure@merck.com
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Scientific contact |
Clinical Trials Disclosure, Merck Sharp & Dohme Corp., ClinicalTrialsDisclosure@merck.com
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Paediatric regulatory details
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Is trial part of an agreed paediatric investigation plan (PIP) |
Yes
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EMA paediatric investigation plan number(s) |
EMEA-000010-PIP01-07 | ||
Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Results analysis stage
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Analysis stage |
Final
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Date of interim/final analysis |
04 Oct 2006
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Is this the analysis of the primary completion data? |
Yes
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Primary completion date |
04 Oct 2006
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Global end of trial reached? |
Yes
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Global end of trial date |
04 Oct 2006
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Was the trial ended prematurely? |
No
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General information about the trial
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Main objective of the trial |
To estimate in pediatric patients, aged 2 to 17 years, with persistent fever and neutropenia, the proportion of participants treated with caspofungin reporting one or more clinical and/or laboratory drug-related adverse experience(s) during the study drug therapy period plus 14 days posttherapy.
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Protection of trial subjects |
This study was conducted in conformance with Good Clinical Practice standards and applicable country and/or local statutes and regulations regarding ethical committee review, informed consent, and the protection of human subjects participating in biomedical research.
If drug-related toxicity develops, the dose may be reduced to the standard dose. Any participant who has a body surface area >=1.2 m^2 is not eligible for dose increase for inadequate clinical response because their standard daily dose of caspofungin approaches the maximum dose of 70 mg/day. Therefore, a participant whose dose in the caspofungin arm is >=60 mg/day (50 mg/m^2 for a 1.2 m^2 participant) and requires dose increase as determined by the investigator, must be discontinued from study therapy.
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Background therapy |
- | ||
Evidence for comparator |
- | ||
Actual start date of recruitment |
28 Apr 2004
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Long term follow-up planned |
No
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Independent data monitoring committee (IDMC) involvement? |
No
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Population of trial subjects
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Number of subjects enrolled per country |
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Country: Number of subjects enrolled |
Germany: 18
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Country: Number of subjects enrolled |
United States: 32
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Country: Number of subjects enrolled |
Spain: 18
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Country: Number of subjects enrolled |
Belgium: 14
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Worldwide total number of subjects |
82
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EEA total number of subjects |
50
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Number of subjects enrolled per age group |
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In utero |
0
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Preterm newborn - gestational age < 37 wk |
0
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Newborns (0-27 days) |
0
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Infants and toddlers (28 days-23 months) |
0
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Children (2-11 years) |
62
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Adolescents (12-17 years) |
20
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Adults (18-64 years) |
0
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From 65 to 84 years |
0
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85 years and over |
0
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Recruitment
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Recruitment details |
- | ||||||||||||||||||
Pre-assignment
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Screening details |
A total of 83 participants were screened. One screened participant was randomized but did not receive study therapy. | ||||||||||||||||||
Period 1
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Period 1 title |
Treatment and Follow-up (overall period)
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Is this the baseline period? |
Yes | ||||||||||||||||||
Allocation method |
Randomised - controlled
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Blinding used |
Double blind | ||||||||||||||||||
Roles blinded |
Subject, Investigator, Carer | ||||||||||||||||||
Arms
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Are arms mutually exclusive |
Yes
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Arm title
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Caspofungin | ||||||||||||||||||
Arm description |
Participants received 1-hour intravenous infusion of caspofungin 70 mg/m^2 as a loading dose on Day 1 followed by 50 mg/m^2 once daily for up to 28 days. On completion of the caspofungin infusion participants received 2-hour intravenous infusion of placebo to liposomal amphotericin B once daily for up to 28 days. Study drug treatment could be for up to 90 days for documented invasive fungal infection. | ||||||||||||||||||
Arm type |
Experimental | ||||||||||||||||||
Investigational medicinal product name |
Caspofungin
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Investigational medicinal product code |
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Other name |
CANCIDAS™, MK-0991
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Pharmaceutical forms |
Solution for infusion
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Routes of administration |
Intravenous use
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Dosage and administration details |
Participants received 1-hour intravenous infusion of caspofungin acetate 70 mg/m^2 as a loading dose on Day 1 followed by 50 mg/m^2 once daily for up to 28 days. Infusion was administered via 1)peripheral line, 2) peripherally inserted central catheter, or 3) other central venous catheter.
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Investigational medicinal product name |
Placebo to Liposomal Amphotericin B
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Solution for infusion
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Routes of administration |
Intravenous use
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Dosage and administration details |
On completion of the caspofungin infusion participants received 2-hour intravenous infusion of placebo to liposomal amphotericin B (5% dextrose in water with multivitamin) once daily for up to 28 days. Infusion was administered via 1 ) peripheral line, 2) peripherally inserted central catheter, or 3) other central venous catheter.
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Arm title
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Liposomal Amphotericin B | ||||||||||||||||||
Arm description |
Participants received 1-hour intravenous infusion of placebo to caspofungin once daily for up to 28 days. On completion of the placebo infusion participants received 2-hour intravenous infusion of liposomal amphotericin B 3.0 mg/kg once daily for up to 28 days. Study drug treatment could be for up to 90 days for documented invasive fungal infection. | ||||||||||||||||||
Arm type |
Active comparator | ||||||||||||||||||
Investigational medicinal product name |
Liposomal Amphotericin B
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Investigational medicinal product code |
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Other name |
AmBisome™
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Pharmaceutical forms |
Solution for infusion
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Routes of administration |
Intravenous use
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Dosage and administration details |
On completion of the placebo infusion participants received 2-hour intravenous infusion of liposomal amphotericin B 3.0 mg/kg once daily for up to 28 days. Infusion was administered via 1)peripheral line, 2) peripherally inserted central catheter, or 3) other central venous catheter.
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Investigational medicinal product name |
Placebo to Caspofungin
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Solution for infusion
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Routes of administration |
Intravenous use
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Dosage and administration details |
Participants received 1-hour intravenous infusion of placebo to caspofungin (0.9% saline) once daily for up to 28 days. Infusion was administered via 1)peripheral line, 2) peripherally inserted central catheter, or 3) other central venous catheter.
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Notes [1] - The number of subjects at this milestone seems inconsistent with the number of subjects in the arm. It is expected that the number of subjects will be greater than, or equal to the number that completed, minus those who left. Justification: Participants who completed study therapy and continued to follow-up [2] - The number of subjects at this milestone seems inconsistent with the number of subjects in the arm. It is expected that the number of subjects will be greater than, or equal to the number that completed, minus those who left. Justification: Participants who completed study therapy and continued to follow-up |
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Baseline characteristics reporting groups
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Reporting group title |
Caspofungin
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Reporting group description |
Participants received 1-hour intravenous infusion of caspofungin 70 mg/m^2 as a loading dose on Day 1 followed by 50 mg/m^2 once daily for up to 28 days. On completion of the caspofungin infusion participants received 2-hour intravenous infusion of placebo to liposomal amphotericin B once daily for up to 28 days. Study drug treatment could be for up to 90 days for documented invasive fungal infection. | ||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Liposomal Amphotericin B
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Reporting group description |
Participants received 1-hour intravenous infusion of placebo to caspofungin once daily for up to 28 days. On completion of the placebo infusion participants received 2-hour intravenous infusion of liposomal amphotericin B 3.0 mg/kg once daily for up to 28 days. Study drug treatment could be for up to 90 days for documented invasive fungal infection. | ||||||||||||||||||||||||||||||||||||||||||||
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End points reporting groups
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Reporting group title |
Caspofungin
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Reporting group description |
Participants received 1-hour intravenous infusion of caspofungin 70 mg/m^2 as a loading dose on Day 1 followed by 50 mg/m^2 once daily for up to 28 days. On completion of the caspofungin infusion participants received 2-hour intravenous infusion of placebo to liposomal amphotericin B once daily for up to 28 days. Study drug treatment could be for up to 90 days for documented invasive fungal infection. | ||
Reporting group title |
Liposomal Amphotericin B
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Reporting group description |
Participants received 1-hour intravenous infusion of placebo to caspofungin once daily for up to 28 days. On completion of the placebo infusion participants received 2-hour intravenous infusion of liposomal amphotericin B 3.0 mg/kg once daily for up to 28 days. Study drug treatment could be for up to 90 days for documented invasive fungal infection. |
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End point title |
Percentage of Participants with One or More Drug-related Adverse Experience [1] | ||||||||||||||||||
End point description |
An adverse experience is defined as any unfavorable and unintended change in the structure, function, or chemistry of the body temporally associated with the use of the sponsor's product, whether or not considered related to the use of the product. Any worsening of a preexisting condition which is temporally associated with the use of the sponsor's product, is also an adverse experience. Drug-related adverse experiences were those determined by the investigator to be possibly, probably, or definitely drug related. The population included all participants who received at least one dose of active study therapy.
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End point type |
Primary
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End point timeframe |
Up to 14 days after the end of study therapy
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Notes [1] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: No between-group statistical analyses were planned for the study. |
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No statistical analyses for this end point |
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End point title |
Percentage of Participants with One or More Drug-related Serious Adverse Experiences | ||||||||||||||||||
End point description |
A serious adverse experience is any adverse experience that results in death, is life threatening, results in persistent or significant disability or incapacity, results in or prolongs an existing inpatient hospitalization, is a congenital anomaly or birth defect, is a cancer, or is an overdose. Drug-related adverse experiences were those determined by the investigator to be possibly, probably, or definitely drug related. The population included all participants who received at least one dose of active study therapy.
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End point type |
Secondary
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End point timeframe |
Up to 14 days after the last dose of study therapy
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No statistical analyses for this end point |
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End point title |
Percentage of Participants Who Discontinued Study Therapy due to a Drug-related Adverse Experience | ||||||||||||||||||
End point description |
An adverse experience is defined as any unfavorable and unintended change in the structure, function, or chemistry of the body temporally associated with the use of the sponsor's product, whether or not considered related to the use of the product. Any worsening of a preexisting condition which is temporally associated with the use of the sponsor's product, is also an adverse experience. Drug-related adverse experiences were those determined by the investigator to be possibly, probably, or definitely drug related. The population included all participants who received at least one dose of active study therapy.
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End point type |
Secondary
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End point timeframe |
Up to the last dose of study therapy
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No statistical analyses for this end point |
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End point title |
Percentage of Participants with Favorable Overall Efficacy Outcome | ||||||||||||
End point description |
Favorable overall efficacy outcome was defined as meeting each of the following criteria: 1) survival for >=7 days after end of study drug therapy, 2) resolution of fever during the period of neutropenia, 3) for participants with a fungal infection at baseline, successful treatment of the baseline infection, 4) absence of breakthrough fungal infections during administration of study drug or within 7 days after the end of treatment, and 5) absence of premature discontinuation of the study drug because of study-drug-related toxicity or lack of efficacy. The population included participants who received chemotherapy for hematological or solid organ malignancies or hematopoietic stem cell transplant, met the protocol-defined inclusion criteria for fever and neutropenia, and received at least 1 dose of study therapy.
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End point type |
Secondary
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End point timeframe |
Up to 7 days after the last dose of study therapy
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No statistical analyses for this end point |
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Adverse events information
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Timeframe for reporting adverse events |
Up to 14 days after the last dose of study drug
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Adverse event reporting additional description |
Although a participant may have had two or more clinical adverse events, the participant is counted only once within a category. The same participant may appear in different categories.
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Assessment type |
Systematic | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary used for adverse event reporting
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Dictionary name |
MedDRA | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary version |
9.1
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Reporting groups
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Reporting group title |
Caspofungin
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Reporting group description |
Participants received 1-hour intravenous infusion of caspofungin 70 mg/m^2 as a loading dose on Day 1 followed by 50 mg/m^2 once daily for up to 28 days. On completion of the caspofungin infusion participants received 2-hour intravenous infusion of placebo to liposomal amphotericin B once daily for up to 28 days. Study drug treatment could be for up to 90 days for documented invasive fungal infection. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Liposomal Amphotericin B
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Reporting group description |
Participants received 1-hour intravenous infusion of placebo to caspofungin once daily for up to 28 days. On completion of the placebo infusion participants received 2-hour intravenous infusion of liposomal amphotericin B 3.0 mg/kg once daily for up to 28 days. Study drug treatment could be for up to 90 days for documented invasive fungal infection. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Frequency threshold for reporting non-serious adverse events: 5% | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Substantial protocol amendments (globally) |
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Were there any global substantial amendments to the protocol? No | |||
Interruptions (globally) |
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Were there any global interruptions to the trial? No | |||
Limitations and caveats |
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Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data. | |||
None reported |